Both hormonal and genetic factors determine the sexual differentiation and development of mammalian brain. As a focus for both of these influences, we shall examine the ontogeny and macromolecular interactions of putative sex steroid receptors in developing mouse brain. Presumed receptors for estrogens and androgens will be detected, quantitated and qualitatively characterized by DNA-cellulose affinity chromatography. Inbred strains of normal mice and the androgen-resistant mutant, testicular feminization (Tfm) will be compared in order to probe the genetic determination and regulation of these steroid-binding proteins which are presumed to detect the levels of different sex steroids. The Tfm mutant, which is deficient in its androgen receptor level, will be utilized as both a negative, genetic control and for the purpose of defining more completely the biochemical nature of one particular androgen-response mutant. As such, this description should provide useful information for efforts to understand and manage similar syndromes that occur in humans. In parallel with biochemical and genetic studies of the estrogen receptor proteins, we shall culture cells from mouse hypothalamus to establish a system in which steroid responses of the hypothalamus can be observed at a cellular level.